Case Report Intrathecal Trastuzumab for Meningeal Carcinomatosis ...

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360 Y. H. Chen et al./JCOS 25(2009) 357-364Table 1. Clinical course of intrathecal trastuzumab for menigeal carcinomatosis, and CSF analysisDate Glucose (mg/dl) Total protein (mg/dl) Cytology Intrathecal trastuzumabApril 43 on 4/13, 932 on 4/13,Positive malignancy _78 on 4/15 38.2~68.3 of eightsamplesof 4/13, 4/15, 4/17,4/19, 4/21, 4/24,4/26, 4/28, 4/30May 74~95 during5/7, 5/11, 5/14,15.1~57.2 of elevensamplesPositive malignancyon 5/01,5/03, and20 mgon 5/8, 5/12, 5/15, 5/19,5/25June5/23, 5/25_ 37.8 on 6/2negative findingfrom May to November20 mg on 6/2, 6/9, 6/17, 6/24July _ 11.4~50.6 of tensamples(the last lumbarpuncture: 11/7)20 mg on 7/1, 7/8, 7/1860 mg on 7/2180 mg on 7/27August 76.7~101.3 during8/1, 8/3 , 8/2813~21.4 of sixsamples100 mgon 8/3, 8/10, 8/17, 8/25September _ _ 100 mg on 9/185 mg on 9/8, 9/15, 9/22, 9/29October _ _ 85 mgon 10/6, 10/13, 10/20, 10/27November 87.2 on 11/6 58.3 on 11/6, 40.8 on85 mg on 11/411/7CSF aspiration from Ommaya to reduce IICP freqencyAfter aspiration, we send CSF samples for evaluation, and intrathecal trastuzumab was given via OmmayaIn July, we modified trastuzumab dose gradually and no obvious side effect was notedtransient and limited to radiological findings [14].Takashi et al. reported on successful treatment ofleptomeningeal metastases from breast cancer usingthe combination of intravenous trastuzumab and capecitabine[26]. But the activity of intravenous trastuzumabfor leptomeningeal metastases remains controversial.Lapatinib, which is a‘small molecule’ (50% volumetric reduction of CNS lesions was observedin 19/241 (7%) of patients with lapatinib alone[31].Intrathecal administration of trastuzumab is a moreindividual approach of treatment for leptomeningealcarcinomatosis. As demonstrated in Table 2, six casereports of treatment of meningeal carcinomatosis byintrathecal trastuzumab combined with intrathecalthiotepa [16,18,21] or methotrexate [17-19,21] werereported [16-21]. It was difficult to evaluate the effectivenessof intrathecal trastuzumab, as symptoms oftentook several weeks to clearly improve. As demonstratedin Table 1, major clinical improvement observedin our patient was not reflected by changes inCSF proteins. Less association between CSF proteinsand trastuzumab dose was also noted. Despite beinglarger than trastuzumab in size, CA 153 can cross thealtered blood-brain barrier. However, the concentration
Y. H. Chen et al./JCOS 25(2009) 357-364 361Table 2. Previously published experience of intrathecal trastuzumab for menigeal carcinomatosisAge;Metastasis;Target therapybefore LMdiagnosisTreatment after LM Best response Survivalsinceintrathecaltrastuzumab41 y/o;Peritonealcarcinomatosis;i.v. trastuzumab40 y/o;Solitary CNSmetastasis;Nil.48 y/o;T5-9 epiduralmass, lung, brainmetastasis;i.v. trastuzumab53 y/o;Terminal cone,Lung, brain, liver;i.v. trastuzumab,lapatinib58 y/o;multiple brainmetastasis;i.v. trastuzumab38 y/o;Liver, brainmetastasis;i.v. trastuzumab57 y/o;Liver, lung, brainmetastasis;i.v. trastuzumab ,lapatinibIntrathecal trastuzumab 20 mg weekly,i.v. paclitaxel + iv. trastuzumabIntrathecal trastuzumab 20 mg weekly,i.v. liposomal doxorubicin + trastuzumabIntrathecal trastuzumab 20 mg weekly,intrathecal prednisone + thiotepai.v. trastuzumab + capecitabine, intrathecalmethotrexateIntrathecal trastuzumab 5~20 mg twiceweeklyi.v. trastuzumab + vinorelbine, intrathecalmethotrexatei.v. trastuzumab + vinorelbine,Intrathecal trastuzumab 5~20 mg +alternating intrathecal methotexate andthiotepaLapatinib, then i.v. gemcitabine + cisplatin+ trastuzumabIntrathecal trastuzumab 20 mg + intrathecalmethotrexate 12 mg, Every 3~6 daysIntrathecal trastuzumab 20,40,100,100,100,100 mgweekly x total 6 timesIntrathecal 20~30 mg trastuzumab weekly xtotal 8 times(combined intrathecal MTX 10 mg x2times, iv PLD)intrathecal 40~50 mg trastuzumab Every 3weeks(December 2006~ August 2008, combinedintrathecal thiotepa 10~12 mg , i.v.trastuzumab , PLD, vinorelbine, paclitaxel )Intrathecal MTX 12 mg x 3 timesIntrathecal 20~60 mg trastuzumab every3~7 days x total 13 times,Intrathecal high- dose (80~100) trastuzumabweekly x total 15 times (combined oralcyclophosphamide)PDclinical progression,but CSFresponseClinical impreovement,CSFresponsePDClinical improvement,CSFresponseClinical SDClinical SDPDClinical improvement,CSFresponseClinicalimprovement, SD on MRIClinicalimprovement,CSF response,PR on MRISDClinical improvement,CSFresponse21 months 165.2 months 1730 days 18
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